Human gut microbiota produce a variety of molecules, some of which enter the bloodstream and impact health. Conversely, dietary or pharmacological compounds may affect the microbiota before entering ...the circulation. Characterization of these interactions is an important step towards understanding the effects of the gut microbiota on health. In this cross-sectional study, we used deep metagenomic sequencing and ultra-high-performance liquid chromatography linked to mass spectrometry for a detailed characterization of the gut microbiota and plasma metabolome, respectively, of 8583 participants invited at age 50 to 64 from the population-based Swedish CArdioPulmonary bioImage Study. Here, we find that the gut microbiota explain up to 58% of the variance of individual plasma metabolites and we present 997 associations between alpha diversity and plasma metabolites and 546,819 associations between specific gut metagenomic species and plasma metabolites in an online atlas ( https://gutsyatlas.serve.scilifelab.se/ ). We exemplify the potential of this resource by presenting novel associations between dietary factors and oral medication with the gut microbiome, and microbial species strongly associated with the uremic toxin p-cresol sulfate. This resource can be used as the basis for targeted studies of perturbation of specific metabolites and for identification of candidate plasma biomarkers of gut microbiota composition.
Although development of microbiota in childhood has been linked to chronic immune-related conditions, early childhood determinants of microbiota development have not been fully elucidated. We used ...16S rRNA sequencing to analyse faecal and saliva samples from 83 children at four time-points during their first 2 years of life and from their mothers. Our findings confirm that gut microbiota in infants have low diversity and highlight that some properties are shared with the oral microbiota, although inter-individual differences are present. A considerable convergence in gut microbiota composition was noted across the first 2 years of life, towards a more diverse adult-like microbiota. Mode of delivery accounted for some of the inter-individual variation in early childhood, but with a pronounced attenuation over time. Our study extends previous research with further characterization of the major shift in gut microbiota composition during the first 2 years of life.
A clustering of cardiovascular risk factors is denoted the metabolic syndrome (MetS), but the mechanistic underpinnings of this clustering is not clear. Using large-scale metabolomics, we aimed to ...find a metabolic profile common for all five components of MetS. 791 annotated non-xenobiotic metabolites were measured by ultra-performance liquid chromatography tandem mass spectrometry in five different population-based samples (Discovery samples: EpiHealth, n = 2342 and SCAPIS-Uppsala, n = 4985. Replication sample: SCAPIS-Malmö, n = 3978, Characterization samples: PIVUS, n = 604 and POEM, n = 501). MetS was defined by the NCEP/consensus criteria. Fifteen metabolites were related to all five components of MetS (blood pressure, waist circumference, glucose, HDL-cholesterol and triglycerides) at a false discovery rate of <0.05 with adjustments for BMI and several life-style factors. They represented different metabolic classes, such as amino acids, simple carbohydrates, androgenic steroids, corticosteroids, co-factors and vitamins, ceramides, carnitines, fatty acids, phospholipids and metabolonic lactone sulfate. All 15 metabolites were related to insulin sensitivity (Matsuda index) in POEM, but only Palmitoyl-oleoyl-GPE (16:0/18:1), a glycerophospholipid, was related to incident cardiovascular disease over 8.6 years follow-up in the EpiHealth sample following adjustment for cardiovascular risk factors (HR 1.32 for a SD change, 95%CI 1.07-1.63). A complex metabolic profile was related to all cardiovascular risk factors included in MetS independently of BMI. This profile was also related to insulin sensitivity, which provide further support for the importance of insulin sensitivity as an important underlying mechanism in the clustering of cardiovascular risk factors.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Appendicular lean mass (ALM) associates with mobility and bone mineral density (BMD). While associations between gut microbiota composition and ALM have been reported, previous studies rely on ...relatively small sample sizes. Here, we determine the associations between prevalent gut microbes and ALM in large discovery and replication cohorts with information on relevant confounders within the population-based Norwegian HUNT cohort (n = 5196, including women and men). We show that the presence of three bacterial species - Coprococcus comes, Dorea longicatena, and Eubacterium ventriosum - are reproducibly associated with higher ALM. When combined into an anabolic species count, participants with all three anabolic species have 0.80 kg higher ALM than those without any. In an exploratory analysis, the anabolic species count is positively associated with femoral neck and total hip BMD. We conclude that the anabolic species count may be used as a marker of ALM and BMD. The therapeutic potential of these anabolic species to prevent sarcopenia and osteoporosis needs to be determined.
Abstract
Objective
The objective was to investigate whether muscle strength in the nonaffected and affected upper extremities (UEs) in children (7–12 years) with unilateral spastic cerebral palsy ...(USCP) differs from that in children with typical development (TD).
Methods
A cross-sectional study design was used. Isometric arm strength (wrist flexion, wrist extension with flexed and extended fingers, elbow flexion/extension) was assessed in 72 children (mean age = 9.3 SD = 1.9 years) with USCP, and isometric grip/pinch strength was assessed in 86 children (mean age = 9.3 SD = 1.8 years) with USCP. Arm/grip/pinch strength was assessed in 120 children (mean age = 9.5 SD = 1.7 years) with TD. Arm strength was measured with a hand-held dynamometer, and grip/pinch strength was measured with a calibrated, modified (digitized) grip dynamometer and a pinch meter. The nonaffected UE of children with USCP was compared with the preferred UE of children with TD because both sides represent the preferred UE. The affected UE was compared with the nonpreferred UE of children with TD, as both sides represent the nonpreferred UE.
Results
In all measurements except for grip strength of the preferred UE, children with USCP were weaker than children with TD.
Conclusions
In children with USCP, muscle strength weakness exists in both UEs.
Impact
When unimanual or bimanual ability limitations are present in children with unilateral cerebral palsy, investigation of the muscle strength of the nonaffected UE should be part of the assessment.
Gut microbiota have been implicated in atherosclerotic disease, but their relation with subclinical coronary atherosclerosis is unclear. This study aimed to identify associations between the gut ...microbiome and computed tomography-based measures of coronary atherosclerosis and to explore relevant clinical correlates.
We conducted a cross-sectional study of 8973 participants (50 to 65 years of age) without overt atherosclerotic disease from the population-based SCAPIS (Swedish Cardiopulmonary Bioimage Study). Coronary atherosclerosis was measured using coronary artery calcium score and coronary computed tomography angiography. Gut microbiota species abundance and functional potential were assessed with shotgun metagenomics sequencing of fecal samples, and associations with coronary atherosclerosis were evaluated with multivariable regression models adjusted for cardiovascular risk factors. Associated species were evaluated for association with inflammatory markers, metabolites, and corresponding species in saliva.
The mean age of the study sample was 57.4 years, and 53.7% were female. Coronary artery calcification was detected in 40.3%, and 5.4% had at least 1 stenosis with >50% occlusion. Sixty-four species were associated with coronary artery calcium score independent of cardiovascular risk factors, with the strongest associations observed for
and
subsp
(
<1×10
). Associations were largely similar across coronary computed tomography angiography-based measurements. Out of the 64 species, 19 species, including streptococci and other species commonly found in the oral cavity, were associated with high-sensitivity C-reactive protein plasma concentrations, and 16 with neutrophil counts. Gut microbial species that are commonly found in the oral cavity were negatively associated with plasma indole propionate and positively associated with plasma secondary bile acids and imidazole propionate. Five species, including 3 streptococci, correlated with the same species in saliva and were associated with worse dental health in the Malmö Offspring Dental Study. Microbial functional potential of dissimilatory nitrate reduction, anaerobic fatty acid β-oxidation, and amino acid degradation were associated with coronary artery calcium score.
This study provides evidence of an association of a gut microbiota composition characterized by increased abundance of
spp and other species commonly found in the oral cavity with coronary atherosclerosis and systemic inflammation markers. Further longitudinal and experimental studies are warranted to explore the potential implications of a bacterial component in atherogenesis.
Abstract
Background
For children with unilateral spastic cerebral palsy (USCP), reduced muscle strength can lead to activity limitations. However, none of the existing measures of upper extremity ...strength measure strength in the context of functional activities in which strength must be maintained for several seconds.
Objective
The objective of this study was to evaluate the psychometric properties of 2 newly developed functional hand and upper extremity muscle-strength tests (Cup-Task and Box-Task) in children aged 7 to 12 years with USCP.
Design
A longitudinal study design was used.
Methods
A standardized protocol with detailed descriptions of all procedures and measurements was used to determine test-retest reliability, interrater reliability, and criterion validity.
Results
A total of 86 children (53 males, 33 females, mean age = 9.3 years) with USCP participated in this study, with a subset performing each measurement. Only the results of children who were able to perform the measurement were included for analysis. Excellent test-retest reliability (intraclass correlation coefficients = 0.887–0.944; 95% confidence intervals = 0.713–0.969) and interrater reliability (intraclass correlation coefficients = 0.896–0.960; 95% confidence intervals = 0.813–0.980) were observed. The Cup-Task Affected-Hand and Box-Task were moderately correlated with maximum isometric grip strength. The Cup-Task Nonaffected-Hand had a low correlation with maximum isometric grip strength.
Limitations
Age, sex, and manual ability were not normally distributed, which could have influenced the results.
Conclusions
For children with USCP who can perform the tasks, the Cup-Task and Box-Task are reliable and valid instruments for measuring functional upper extremity muscle strength.
Epigenetic clocks use DNA methylation (DNAm) levels of specific sets of CpG dinucleotides to accurately predict individual chronological age. A popular application of these clocks is to explore ...whether the deviation of predicted age from chronological age is associated with disease phenotypes, where this deviation is interpreted as a potential biomarker of biological age. This wide application, however, contrasts with the limited insight in the processes that may drive the running of epigenetic clocks.
We perform a functional genomics analysis on four epigenetic clocks, including Hannum's blood predictor and Horvath's multi-tissue predictor, using blood DNA methylome and transcriptome data from 3132 individuals. The four clocks result in similar predictions of individual chronological age, and their constituting CpGs are correlated in DNAm level and are enriched for similar histone modifications and chromatin states. Interestingly, DNAm levels of CpGs from the clocks are commonly associated with gene expression in trans. The gene sets involved are highly overlapping and enriched for T cell processes. Further analysis of the transcriptome and methylome of sorted blood cell types identifies differences in DNAm between naive and activated T and NK cells as a probable contributor to the clocks. Indeed, within the same donor, the four epigenetic clocks predict naive cells to be up to 40 years younger than activated cells.
The ability of epigenetic clocks to predict chronological age involves their ability to detect changes in proportions of naive and activated immune blood cells, an established feature of immuno-senescence. This finding may contribute to the interpretation of associations between clock-derived measures and age-related health outcomes.
In order to make inferences about strength related to development or treatment interventions, it is important to use measurement instruments that have sound clinimetric properties.
The objective of ...this review is to systematically evaluate the level of evidence of the clinimetric properties of instruments for measuring upper extremity muscle strength at the "body functions & structures" level of the International Classification of Functioning, Disability and Health for Children and Youth (ICF-CY) for children with cerebral palsy (CP).
A systematic search of the PubMed, EMBASE, OTseeker, CINAHL, PEDro, and MEDLINE databases up to November 2012 was performed.
Two independent raters identified and examined studies that reported the use of upper extremity strength measurement instruments and methods for children and adolescents with CP aged 0 to 18 years.
The COSMIN (COnsensus-based Standards for the selection of health status Measurement INstruments) checklist with 4-point rating scale was used by 2 independent raters to evaluate the methodological quality of the included studies. Best evidence synthesis was performed using COSMIN outcomes and the quality of the clinimetric properties.
Six different measurement instruments or methods were identified. Test-retest, interrater, and intrarater reliability were investigated. Two test-retest reliability studies were rated as "fair" for the level of evidence. All other studies were rated as "unknown" for the level of evidence.
The paucity of literature describing clinimetric properties, especially other than reliability, of upper limb strength measurement instruments for children with CP was a limitation of the study.
For measuring grip strength, the Jamar dynamometer is recommended. For other muscle groups, handheld dynamometry is recommended. Manual muscle testing (MMT) can be used in case of limited (below MMT grade 4) wrist strength or for total upper limb muscle strength. Based on lacking information regarding other clinimetric properties, caution is advised regarding interpretation of the results.
Celotno besedilo
Dostopno za:
DOBA, FSPLJ, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
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